The limited successes in nonhuman primate studies in eliciting protective immunity against the AIDS virus by strategies that are safe for human use suggest that novel technologies may be needed to develop an HIV vaccine. Recent studies in small animal influenza models have indicated that DNA inoculation can induce potent protective anti-viral immunity. The simian immunodeficiency virus of macaques (SIVmac)-infected rhesus monkey has proven a powerful model system for assessing novel AIDS virus vaccine strategies. We will employ the SIVmac/rhesus monkey model to study the use of DNA vaccines for preventing HIV infection. Specifically, we will explore the: 1. Construction of SIVmac DNA vaccine vectors 2. Immunogenicity of these constructs 3. Novel DNA vaccine delivery systems 4. Combined modality immunization employing DNA vaccines 5. Protective immunity achieved through DNA vaccination